By Sharon Begley
NEW YORK, Nov 13 (Reuters) - The first human test of anexperimental vaccine against a deadly strain of avian flu, usingnovel technology that could produce millions of doses veryquickly, produced protective antibodies in the vast majority ofthose who received it, scientists said on Wednesday.
The encouraging results in the early stage trial fromNovavax, a biopharmaceutical company based inRockville, Maryland, were published online in the New EnglandJournal of Medicine.
"These are very preliminary results, but it appears for thefirst time that we may have a vaccine that would work against anoutbreak" of avian flu, said Robin Robinson, director of the Biomedical Advanced Research and Development Authority, orBARDA, the federal agency in charge of developingcountermeasures against public health emergencies.
Because other candidate vaccines against avian flu havefailed, "this is a very important milestone," he said. "We havea promising vaccine where before we had none."
The H7N9 strain of avian flu emerged in China last winter,causing 45 deaths in 137 confirmed cases this year through lateOctober, according to the World Health Organization. Cases anddeaths, often from severe pneumonia, both peaked last March andApril.
But public health experts fear the virus could come stormingback this flu season. After no reported cases of H7N9 in Chinain August or September, there have been four since earlyOctober.
A mortality rate of one-third suggests the virus is highlylethal.
The WHO says there is currently "no indication" the viruscan be transmitted from person to person, and so cannot become apandemic. But flu strains are notorious for undergoing geneticchanges, including those that make them transmissible betweenpeople.
In the clinical trial, conducted in Australia, 284 adultvolunteers received two doses of either a dummy injection(placebo) or one of six formulations of the experimental vaccine- a high or low dose with or without an adjuvant, a chemicalcompound that turbocharges the immune system. The heart of thevaccine is two proteins, dubbed H7 and N9, that stick out fromthe virus and give it its name.
Apart from some redness and soreness around the injectionsite in some volunteers, mostly among those receiving thevaccine containing adjuvant, the vaccine had no ill effects,Novavax reported.
It produced meaningful levels of antibodies, molecules ofthe immune system that attack invaders. The vaccine triggeredproduction of antibodies against the "H" protein in 81 percentof the volunteers who received the vaccine with the high levelof adjuvant, and antibodies against the "N" in more than 90percent.
The study did not expose volunteers to virus, which isconsidered unethical, to see if the antibody levels warded offinfection. "But these antibody levels are very likely to beprotective," said Dr Louis Fries, Novavax's vice president forclinical and medical affairs, who led the study.
Just as important as the vaccine's apparent efficacy is howquickly it can be produced, thanks to eliminating the need touse chicken eggs as most vaccine production does. Fastmanufacturing is important because a pandemic flu strain canemerge with little warning. An initial outbreak of a new flustrain is often followed by a more severe and widespreadoutbreak the following flu season.
That happened with the H1N1 swine flu in early 2009. Vaccinemakers could not produce vaccine before H1N1's "second wave"that autumn, and the virus eventually infected an estimated 61million people in the United States and caused some 12,000deaths, according to the U.S. Centers for Disease Control andPrevention.
But after scientists determined the genetic sequence of H7N9last March, and deposited it in a public database, it tookNovavax only a month to produce an experimental vaccine ready totest in animals. The human volunteers received their first dosesin early July.
"Our technology let us produce vaccine in just a month andstart testing it in four," said Fries.
That was possible because Novavax does not go through thetime-consuming process of using chicken eggs to manufacturevaccine. Instead, it takes the virus' genetic sequence andproduces what it calls a "virus-like particle vaccine."
Virus-like particles, or VLPs, contain three proteins thattrigger the production of antibodies and other immune responsesto thwart the virus. The H and N proteins generate antibodiesthat keep the virus from replicating and infecting cells, whilea third protein stimulates killer T cells to slay any cellsalready infected.
"We think this is two shots on goal on terms of protection"against H7N9 protection, said Fries.
Using Novavax's technique, said BARDA's Robinson, computermodels suggest manufacturers could produce the first doses ofH7N9 vaccine within 12 weeks of the emergence of a pandemic, 50million doses within four months, and hundreds of millions ofdoses within six months.
The trial used two doses, given 21 days apart. Since H7N9 isa new flu strain, it is probable that no one in the generalpopulation carries antibodies to it, said Fries, making twodoses necessary.
Novavax has a three-year, $97 million contract with BARDA todevelop recombinant influenza vaccines and manufacturingcapabilities sufficient to produce enough vaccine for apandemic. It is planning a second trial of the VLP vaccine inearly 2014 to nail down the minimum effective dose, said Fries.
Five other candidate H7N9 vaccines are being developed, saidRobinson, with results expected in four to six months. "If thisone works, the others are likely to as well" because they arebased on similar technology. If so, public health authoritiesaround the world would then likely have multiple vaccines tochoose from should an avian flu pandemic emerge.
- Pharmaceuticals & Drug Trials
- avian flu
- flu season